Microglial activation in Alzheimer's disease: an (R)-[¹¹C]PK11195 positron emission tomography study

Neurobiol Aging. 2013 Jan;34(1):128-36. doi: 10.1016/j.neurobiolaging.2012.04.021. Epub 2012 Jul 26.

Abstract

Inflammatory mechanisms, like microglial activation, could be involved in the pathogenesis of Alzheimer's disease (AD). (R)-[(11)C]PK11195 (1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide), a positron emission tomography (PET) ligand, can be used to quantify microglial activation in vivo. The purpose of this study was to assess whether increased (R)-[(11)C]PK11195 binding is present in AD and mild cognitive impairment (MCI), currently also known as "prodromal AD."

Methods: Nineteen patients with probable AD, 10 patients with prodromal AD (MCI), and 21 healthy control subjects were analyzed. Parametric images of binding potential (BP(ND)) of (R)-[(11)C]PK11195 scans were generated using receptor parametric mapping (RPM) with supervised cluster analysis. Differences between subject groups were tested using mixed model analysis, and associations between BP(ND) and cognition were evaluated using Pearson correlation coefficients.

Results: Voxel-wise statistical parametric mapping (SPM) analysis showed small clusters of significantly increased (R)-[(11)C]PK11195 BP(ND) in occipital lobe in AD dementia patients compared with healthy control subjects. Regions of interest (ROI)-based analyses showed no differences, with large overlap between groups. There were no differences in (R)-[(11)C]PK11195 BP(ND) between clinically stable prodromal AD patients and those who progressed to dementia, and BP(ND) did not correlate with cognitive function.

Conclusion: Microglial activation is a subtle phenomenon occurring in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / pathology*
  • Analysis of Variance
  • Brain Mapping*
  • Carbon Radioisotopes
  • Cluster Analysis
  • Female
  • Humans
  • Isoquinolines*
  • Magnetic Resonance Imaging
  • Male
  • Microglia / diagnostic imaging*
  • Microglia / pathology
  • Middle Aged
  • Positron-Emission Tomography

Substances

  • Carbon Radioisotopes
  • Isoquinolines
  • PK 11195